ABSTRACT The technology to characterize microvascular network dynamics and assess its impact on tissue oxygen delivery is only now emerging. We have recently demonstrated the unprecedented ability to map oxygen in the microvasculature and cerebral tissue with two-photon microscopy (TPM) [Sakadzic2010] and are proposing to complement this with our novel statistical intensity variation optical coherence tomography (OCT), enabling quantitative dynamic maps of microvessel flow, red blood cell flux, and vessel diameter. Combined, these technologies will provide unprecedented spatio-temporal resolution imaging of oxygen delivery to brain tissue. These technologies will have a broad impact in health science in preclinical models of neuro- degenerative diseases and cancer, and, as we elaborate in Aim 4, help guide the identification of clinically relevant imaging biomarkers. To demonstrate the technologies' utility, we will address fundamental questions about cerebral vascular physiology: How do microvascular flow properties impact tissue oxygenation, and how do age-related vascular alterations compromise tissue oxygenation? We will then relate these findings to clinically relevant imaging biomarkers.